| Abstract
| - The use of synthetic oligonucleotides as possible drugs for humantherapy is usually hampered bytheir low in vivo stability and capacity toachieve high concentrations at their cellular targets.Toovercome this, it has been suggested that they be modified chemically.Among the various options,conjugation with short- and long-chain polyethylene glycols (PEGs) hasseveral advantages: PEG isnontoxic and very soluble, reduces immunogenic reactions, and increasesthe stability of the conjugatedmolecules. PEG is generally joined to oligonucleotides while boundto the insoluble solid-phasesupports, after their synthesis, which does not allow for their beingeasy scaled up. The use of theliquid-phase approach as an alternative synthetic process, utilizingthe PEG polymer both as a soluble,inert synthetic support and a stabilizing agent of the oligonucleotide,is proposed. A new protocolhas been set up, characterized by a stable phosphate bond between thesupport and the oligonucleotide.This method has been tested on a 12mer previously investigated asan antisense agent against HIV.The PEG-conjugated 12mer was efficiently synthesized and purified.It was found that the high-molecular mass PEG chain results in enzymatic stability and does notinterfere with the formation ofthe duplex with its nucleic acid target.
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